XB130 is a recently cloned 130 kDa-adaptor protein and is reported to be predominantly expressed in the thyroid and the spleen tissues validated by northern blot and plays a multifunctional role in cell survival, proliferation, invasion in thyroid tumor 
, but its mRNA and protein expression in other tissues has not been confirmed by real-time PCR, western blot or immunohistochemistry. In this article, we firstly gave evidence that XB130 mRNA and protein were also constitutively expressed in normal gastric tissue and relatively lower expression in GC cells. These findings are in contrast with previous reports that XB130 mRNA was barely detectable in other tissues except thyroid and spleen 
, partly because they only used northern blot for confirmation. XB130 expression is reduced in thyroid tumor, but it remains completely unclear whether XB130 is a prognostic biomarker of other malignant tumors such as gastric cancer (GC) 
. In order to confirm that XB130 takes part in the GC progression, we had analyzed survival or recurrence in 411 patients with GC and noted that the XB130 low expression predicted a lower survival and higher recurrence. Furthermore, Chemotherapeutic sensitivity basing on XB130 expression was evaluated for the first time, and cellular experiments and clinical retrospective study indicated that downregulation of XB130 increases drug sensitivity to cisplatin and irinotecan and decreases drug sensitivity to 5-fluorouracil.
Given the carcinogenicity in previous reports 
, XB130 should be regarded as an oncogenic other than a tumor-suppressive protein, although further studies are needed to test whether it is also the case in GC. Then, how to explain the clinical significance of our clinical observation that XB130 downregulation predicts a low overall survival in advanced GC and higher recurrence rate in patients treated by radical resection surgery? In fact, it is known that tumorigenesis can result from alterations of multiple genes and proteins, while XB130, the adaptor protein with more than one functional domain, can be affected by multiple upstream and downstream factors. Therefore, it is too premature to judge whether a gene or a protein is oncogenic or not just basing on its expression in clinical specimens, although the latter did hint some clues. Actually, downregulation of XB130 in GC may be considered a compensatory adjustment, because some tumor suppressors would be mobilized to resist XB130 during the progression of GC. Similarly, it was reported that the tumor suppressor p53 expression was higher in poorly-differentiated GC than in well-differentiated ones 
, while in early gastric cancers with low levels of apoptosis, increased expression of Bcl-2 and p53 was more likely to promote metastasis 
XB130 may be a proto-oncogene, which preserves in normal tissue. Such proto-oncogenes may contribute to maintain physical functions of cell renewal and upward migration in normal stomach. Meanwhile, there is another set of regulating genes that prevent normal cell over-proliferation and metaplasia. However, once the microecological balance is disequilibrated, cell proliferation and metastasis is out of control, consequently leading to carcinogenesis 
. This classical theory of proto-oncogene may give an acceptable explanation why normal tissue with such high XB130 expression still remains “healthy”. It is known that many genes and signaling pathways play pro-oncogenic or anti-oncogenic roles on a context-dependent manner, so it is not uncommon that the same gene may exert different effect at different stages or in different tissue types of cancer development 
. In the present study, although we did not touch upon the functions of XB130 in normal gastric tissue, this topic is interesting as well and need further research.
If XB130 expression pattern can serve as a surrogate marker predictive of chemotherapy response, it would also provide an explanation for the prognosis. Currently, fluoropyrimidine derivatives-based and platinum compound-based combination regimens have been accepted as conventional first line treatment for GC 
, while irinotecan, a topoisomerase I inhibitor, is employed as the second-line treatment 
, and cisplatin has been largely used in the treatment of advanced, unresectable GC 
. In the present research, chemotherapeutic-sensitivity studies basing on XB130 expression level were carried out. In GC cells, XB130 knockdown indicated better responsiveness to cisplatin and irinotecan, but with less sensitivity to 5-FU. Our clinical data showed a shorter overall survival time in 5-FU-treated patients with low expression of XB130, suggesting that XB130 downregulation reduces the responsiveness to 5-FU, which may be another explanation for the poor prognosis in patients with low expression of XB130 in this study. Our findings in GC cell line implicate that in advanced GCs, most of which are featured by XB130 low expression, may benefit more from cisplatin and irinotecan other than 5-FU. Given the heterogeneous genomic background such as the different expression of XB130 in GC, it is possible that some populations might benefit from irinotecan and/or cisplatin as it suggested in our cellular experiment, and is worthwhile for further investigation. Further prospective investigations may determine whether XB130 expression patterns can be employed to help stratify patients into different multimodal treatment regimens.
In summary, our present study has provided first evidence that XB130 existence in gastric tissue and GC for the first time. We verified that chemotherapeutic sensitivity evaluation basing on XB130 expression was firstly directed, indicating that XB130 low expression patients might be sensitive to cisplatin and irinotecan, yet senior evidence requires. The clinical prospective of this study includes (1) XB130 may act as GC prognostic biomarker for its low expression implicating for unfavorable outcomes; (2) Since XB130 low expressed GC are responsive to cisplatin and irinotecan superior to 5-fluorouracil in our chemotherapeutic sensitivity study, assessment of XB130 expression may help guide clinical medication in GC.